rs6701221

Positions:

• chr1-152806082-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178351.4(LCE1C):​c.-21+519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,158 control chromosomes in the GnomAD database, including 2,578 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2578 hom., cov: 32)
• Consequence: LCE1C NM_178351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894

Genes affected

LCE1C (HGNC:29464): (late cornified envelope 1C) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCE1C	NM_178351.4	c.-21+519G>A		intron_variant		ENST00000607093.2	NP_848128.1
LCE1C	NM_001276331.2	c.-21+519G>A		intron_variant			NP_001263260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCE1C	ENST00000607093.2	c.-21+519G>A		intron_variant			NM_178351.4	ENSP00000475270	P1
LCE1C	ENST00000606576.1	c.-21+519G>A		intron_variant		3		ENSP00000476034

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26790 AN: 152040 Hom.: 2567 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.176 AC: 26830 AN: 152158 Hom.: 2578 Cov.: 32 AF XY: 0.176 AC XY: 13059 AN XY: 74396

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.193

Alfa AF: 0.151 Hom.: 1506

Bravo AF: 0.177

Asia WGS AF: 0.182 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.0
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6701221; hg19: chr1-152778558;